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OHONBocO OSH 2 NO 2 SOO Ni ii iiiONBocONBocB 2OO OSO NHNBocN 33:1+OO OS NHON 3NBocReaction conditions: i:HCO 2 H, ClSO 2 N=C=O, 2,6-lutidine(5 eq), CH 3 CN; ii:Rh 2 (OAc) 4 (5 mol%), PhIO(1.2 eq), 3Å m.s., CH 3 CN, -10°C, 10h; iii: TBAF cat.,TMSN 3 , THF, 10h, rt.Route 3: The aldehyde C was prepared from (S)-glycidol in 7 steps in 53% overall yield.The primary alcohol was first protected. The epoxide ring was opened with sodium azide.Hydrogenolysis of this azide with10% Pd/C gave quantitatively theamine which was reacted withBis-N,N'-Boc methylisothioureato yield the protected guanidine.The cyclic guanidine wasobtained after activation of thesecondary hydroxyl groupfollowed by sodium hydridetreatment. Deprotection of the acetal by acidolysis and oxidation of the alcohol gave thealdehyde C. All the reactions of this sequence gave quantitative yields except the oxidationstep which performed poorly, the best yield (32%) being obtained with NMO/TPAP. Thealdol reaction between C and Z-Gly-OEt was tested using various bases without success.However using lithium diisopropylamine and the Garner aldehyde, which is structurallysimilar to C, the desired condensation product was isolated in 58% yield.Assuming that the poor yields of the oxidation and aldol steps were due to the basicityOReaction conditions : i : DHP (2 eq), APTS cat, CH 2 Cl 2 , 10h, rt; N 3 Na (2 eq), NH 4 Cl (2 eq),EtOH, H 2 O (6/1), 3h, reflux; iii : 10% Pd/C, H 2 , THF, 10h, rt; iv: BocN=(SMe)NHBoc (1.5 eq),CH 2 Cl 2 , 10h, rt; v : MsCl (1.1 eq), Et 3 N (1.5 eq), 10h, rt; vi : NaH (1 eq), DMF, 10h, rt; vii :PTSA(1.1 eq), MeOH, rt; viii : NMO (2 eq), TPAP cat, CH 2 Cl 2 10h, rt.of the guanidine, we decided to perform the aldol reaction prior to the elaboration of theguanidino function. The aldehyde D was prepared from (S)-glycidol in 5 steps in a 74%overall yield.OOHN 3NHOOHOTBSOTBSOTBSOTHP N 3 OTHP N 3 OH N 3 Oi ii iiiDReaction conditions: i : TBSOTf (2 eq), 2, 6-lutidine (2.5 eq), CH 2 Cl 2 , 10h, rt; ii: PPTS cat,MeOH, 2 days, rt; iii: IBX (1.2 eq), DMSO, 10h, rt.The first attempt to run the aldol reaction with Z-Gly-OEt and D (1 eq) using LDA (2 eq) at-78°C gave the condensation product in 28% yield. Optimisation of the conditions of thealdol reaction is under progress as well as the elaboration of the guanidine ring.This last approach seems to be the shortest and mostOTBSpromising way to obtain both enantiomers of the desiredNOTBSOH3amino acid needed to perform the synthesis of the N 3 Omannopeptimycin core.BocHN CO 2 EtAcknowledgmentM. M. thanks ICSN-CNRS for a doctoral fellowship.HOH 2 NHNOHReferences1. He, H., et al. J. Am. Chem. Soc. 124, 9729-9736 (2002).2. During the course of our studies two syntheses were published: Schwörer, C. J., Oberthür, M. Eur. J.Org. Chem 6129-6139 (2009); Olivier, K.S., Van Nieuwenhze, M.S. Org. Lett. 12,1680-1683 (2010).3. Dauban, P., Dodd, R.H. Synlett 1571-1586 (2003); Karila, D., Dodd, R.H. Curr. Org. Chem in press.NHN 3OROOHH OMsOH i, ii iii, iv, vBocHN N OTHP vi, vii BocNN 3 OTHPNBocHNHODP 2 N OR'BocN NHBocN + P 2 HNOCBocNDN 3OHO + P 2 HN CO 2 R'OHCO 2 R'viii BocNHNBocNCO153